Flexible biological fluid filters

ABSTRACT

Filter assemblies are processing biological fluid, such as blood or a blood component containing leukocytes. The filter assemblies include a flexible housing with first and second walls. A filtration medium and a support member are at least partially positioned between the walls of the housing, with a seal joining the walls of the housing, the filtration medium, and the support member. The filter assemblies may further include a pre-filter and/or a post-filter positioned between the walls of the housing. If provided, the pre- and post-filter may be positioned on opposite walls of the filtration medium, with the post-filter being a mesh positioned between the filtration medium and one of the walls of the housing or within an opening defined by the support member. A seal of the filter assembly may pass through the filtration medium, with the filtration medium being substantially omitted in a section of the seal.

FIELD OF THE DISCLOSURE

The present disclosure generally relates to filters used in thecollection and processing of blood and blood components or otherbiological fluids. More particularly, the present disclosure relates toflexible “soft housing” filters and methods for manufacturing suchfilters.

DESCRIPTION OF RELATED ART

Using various manual and automated systems and methods, whole blood iscollected and separated into its clinical components (typically redblood cells, platelets, and plasma). The collected components aretypically individually stored and used to treat a variety of specificconditions and diseased states.

Before transfusing the collected blood components to a recipient in needof the components, or before subjecting blood components to treatment(such as, but not limited to, pathogen inactivation), it is oftendesirable to minimize the presence of impurities or other materials thatmay cause undesired side effects in the recipient. For example, becauseof possible reactions, it is generally considered desirable to reducethe number of leukocytes in blood components before storage, or at leastbefore transfusion (i.e., “leukoreduction”).

Filters are widely used to accomplish leukoreduction in blood productstoday (e.g., warm and cold filtration of leukocytes from whole blood,red cells, and/or platelet products). Filters typically include a filtermedia disposed between mating walls of a filter housing. Inlet andoutlet ports associated with the housing provide flow paths to and fromthe interior of the filter. The walls of the housing may be made of arigid, typically plastic, material, although filters including softhousings are also known. Soft housing filters provide the advantage ofbeing able to withstand handling and centrifuging without breakage ofthe filter. Examples of soft housing filters are disclosed in U.S. Pat.No. 6,367,634; U.S. Pat. No. 6,422,397; U.S. Pat. No. 6,745,902; U.S.Pat. No. 7,353,956; U.S. Pat. No. 7,332,096; U.S. Pat. No. 7,278,541;and U.S. Patent Application Publication No. 2003/0209479, all of whichare hereby incorporated by reference herein. Due to the importance offiltering blood or blood components, there exists an ongoing desire toimprove the construction, performance, and manufacturability ofbiological fluid filters.

SUMMARY

There are several aspects of the present subject matter which may beembodied separately or together in the devices and systems described andclaimed below. These aspects may be employed alone or in combinationwith other aspects of the subject matter described herein, and thedescription of these aspects together is not intended to preclude theuse of these aspects separately or the claiming of such aspectsseparately or in different combinations as set forth in the claimsappended hereto.

In one aspect, a biological fluid filter assembly is provided. Thefilter assembly includes a flexible housing having first and secondwalls. A filtration medium is at least partially positioned between thefirst and second walls of the housing. A seal passes through thefiltration medium to define a perimeter within the biological fluidfilter assembly and joins the first and second walls of the housing,with there being substantially no filtration medium present in a centralsection of the seal along at least a majority of the extent of theperimeter defined by the seal.

In another aspect, a biological fluid filter asembly is provided. Thefilter assembly includes a flexible housing having first and secondwalls. A filtration medium is at least partially positioned between thefirst and second walls of the housing. A post-filter mesh is at leastpartially positioned between the filtration medium and the secondhousing wall. A seal joins the first and second walls of the housing.

In yet another aspect, a biological fluid filter assembly is provided.The filter assembly includes a flexible housing having first and secondwalls, the first wall including an inlet port and the second wallincluding an outlet port, with the first and second walls being made ofa plastic material. A filtration medium for removing at least onesubstance from a biological fluid is at least partially positionedbetween the inlet and outlet ports, with a pre-filter at least partiallypositioned between the inlet port and the filtration medium. A meshelement having a mesh integrally formed with a frame is at leastpartially positioned between the outlet port and the filtration medium,with the mesh element being made of the plastic material. A seal isformed by integrating a section of the filtration medium at or adjacentto its perimeter, a section of the pre-filter at or adjacent to itsperimeter, a section of the frame of the mesh element, and a section ofthe first and second walls at or adjacent to their perimeter and overtheir entire perimeter. The seal includes a central section consistingof a layer consisting only of the plastic material of the first wall andhaving a thickness in the range of approximately 90-100 micrometers, anintermingled layer in which the plastic material of at least the firstwall is intermingled with the pre-filter and having a thickness in therange of approximately 170-200 micrometers, and an aggregate in whichthe plastic material of at least the second wall and the frame areintermingled and having a thickness in the range of approximately840-900 micrometers.

In another aspect, a biological fluid filter asembly is provided. Thefilter assembly includes a flexible housing having first and secondwalls. A filtration medium is at least partially positioned between thefirst and second walls of the housing. A post-filter mesh is at leastpartially positioned between the filtration medium and the secondhousing wall and has a Darcy's Law permeability constant in the range of293 to approximately 5852 μm². A seal joins the first and second wallsof the housing.

In another aspect, a method is provided for manufacturing a biologicalfluid filter assembly. The method includes providing a first flexiblehousing wall and a second flexible housing wall. At least a portion of afiltration medium is positioned between the housing walls. A seal thatpasses through the filtration medium is formed to join the housing wallsand define a perimeter within the biological fluid filter assembly, withthere being substantially no filtration medium present in a centralsection of the seal along at least a majority of the extent of theperimeter defined by the seal.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a front elevational view of a biological fluid filter assemblyaccording to an aspect of the present disclosure;

FIG. 2 is a perspective, exploded view of the biological fluid filterassembly of FIG. 1;

FIG. 3 is a front elevational view of a support member of the biologicalfluid filter assembly of FIG. 1;

FIG. 3A is a front elevational view of the support member of FIG. 3,incorporating a post-filter;

FIG. 4 is a side cross-sectional view of a portion of the biologicalfluid filter assembly of FIG. 1;

FIG. 5 is a side cross-sectional view of a portion of another embodimentof a biological fluid filter assembly according to an aspect of thepresent disclosure;

FIGS. 6A-6C illustrate steps of an exemplary process for manufacturingbiological fluid filter assemblies according to the present disclosure;

FIGS. 7A-7C illustrate steps of another exemplary process formanufacturing biological fluid filter assemblies according to thepresent disclosure;

FIG. 8 is a cross-sectional view of a sealing die according to knowndesign that may be used to form an inner seal of a biological fluidfilter assembly according to the present disclosure;

FIG. 9 is a cross-sectional view of a sealing die that may be used toform an inner seal substantially omitting filtration medium in a sectionthereof;

FIG. 10 is a detail view of a section of a biological fluid filterassembly prior to forming an inner seal; and

FIG. 11 is a cross-sectional view of the section of the biological fluidfilter assembly of FIG. 10, after having formed an inner sealsubstantially omitting filtration medium in a section thereof; and

FIG. 12 is a cross-sectional view of an alternative sealing die that maybe used to form an inner seal substantially omitting filtration mediumin a section thereof.

DESCRIPTION OF THE ILLUSTRATED EMBODIMENTS

The embodiments disclosed herein are for the purpose of providing adescription of the present subject matter, and it is understood that thesubject matter may be embodied in various other forms and combinationsnot shown in detail. Therefore, specific embodiments and featuresdisclosed herein are not to be interpreted as limiting the subjectmatter as defined in the accompanying claims.

FIG. 1 shows an exemplary embodiment of a biological fluid filterassembly 10 according to the present disclosure. As shown in FIG. 1, thefilter assembly 10 may include an outer housing having first and secondsides or walls 12 and 14 (FIGS. 2 and 4), which may correspond to inletand outlet sides for fluid flowing through the filter assembly 10. Inone embodiment, the first and second walls 12 and 14 of the filterhousing may be separate sheets of flexible material (FIGS. 2 and 6A-6C),which may be formed of a polyvinyl chloride (“PVC”) material or anyother suitable material (preferably a flexible, medical grade plasticmaterial) through which the biological fluid will not flow. In anotherembodiment, the first and second walls 12 and 14 of the filter housingmay be opposing faces of a generally tubular piece of material 16 (FIGS.7A-7C) or two portions of a single sheet of material that is folded ontoitself.

Preferably, the inlet or first side 12 of the filter housing is providedwith an inlet port 18 (FIGS. 1 and 2) and the outlet or second side 14of the filter housing is provided with an outlet port 20 (FIGS. 1 and4), with the ports 18 and 20 positioned at least partially outside ofthe filter assembly 10 for connection to other components of a fluidprocessing set by tubing or the like. The inlet and outlet ports 18 and20 may be secured to their associated walls of the filter housing by anysuitable means (e.g., being heat sealed thereto using radio-frequencyenergy). The walls 12 and 14 of the filter housing are preferably eachprovided with an opening or aperture with which the associated portcommunicates to allow fluid flow into and out of the filter assembly 10.FIG. 2 shows an opening 22 formed in the first wall 12 and FIG. 4 showsan opening 24 formed in the second wall 14 of the filter housing.

In the embodiment of FIG. 4, the outlet port 20 includes an extension orprojection or formation or spacer 26 which passes through the associatedopening 24 and into an interior of the filter assembly 10. If provided,the spacer 26 may serve to space or separate the outlet side 14 of thefilter housing from an interior component of the filter assembly 10(such as a filtration medium) to prevent the interior component frombeing pulled into contact with the outlet side 14 during filtration (dueto a pressure differential), which can hinder fluid flow through thefilter assembly 10. Alternatively, a outlet port 28 may be providedwithout a spacer (FIG. 5), in which case the filter assembly may or maynot include a separate spacer positioned within the filter assembly,adjacent to the outlet side 14 of the filter housing to separate theoutlet side 14 from an interior component of the filter assembly.

The inlet and outlet ports 18 and 20, 28 are preferably relatively rigidcompared to the filter housing, and may comprise molded componentsformed of a plastic material, although other materials and manufacturingmethods may be employed without departing from the scope of the presentdisclosure.

A filtration medium 30 (FIGS. 2 and 4) is at least partially positionedbetween the two walls 12 and 14 of the filter housing. Preferably, thefiltration medium 30 is fully positioned within the filter housing whenthe filter assembly 10 is fully assembled, as in FIG. 1.

The filtration medium 30 may be variously configured, depending on thenature of the substance(s) to be removed or separated from thebiological fluid passed through the filter assembly 10. For example, thefiltration medium 30 may be configured to remove a substance orsubstances from a biological fluid by depth filtration or by a bindingmaterial that retains the targeted substance(s) while allowing the othercomponents of the biological fluid to flow through the filtration medium30. In an exemplary embodiment, the filtration medium 30 is configuredto separate leukocytes from blood or a blood component or some otherleukocyte-containing fluid by depth filtration, in which case thefiltration medium 30 may be formed of a fibrous or non-fibrous materialhaving pores sized to trap leukocytes within the filter assembly 30,while allowing other components of the biological fluid to pass through.The filtration medium 30 may be formed of any suitable material but, inone exemplary embodiment, is formed of a melt-blown, nonwoven, fibrousmaterial, such as a polybutylene terephthalate (“PBT”) material.

In one embodiment, the filtration medium 30 is formed from a pluralityof layers, which may be either substantially identical or differentlyconfigured. For example, a multi-layer filtration medium may becomprised of a plurality of fibrous layers, a plurality of non-fibrouslayers, or a combination of fibrous layers and non-fibrous layers. Whilea multi-layer filtration medium may be preferred for improved filtrationperformance, it is also within the scope of the present disclosure forthe filtration medium to be a single-layer component.

In addition to a filtration medium 30, at least a portion of a supportmember may also be positioned between the walls 12 and 14 of the filterhousing. Preferably, the support member is fully positioned within thefilter housing when the filter assembly 10 is fully assembled (as inFIG. 1), between the filtration medium 30 and the outlet or second side14 of the filter housing.

The support member may be variously configured, but in the embodiment ofFIGS. 1-4, the support member is provided as a frame 32. The frame 32may be variously configured, but is preferably configured as a planar orsheet-like component with an outer perimeter having a shape that iscongruent to the filtration medium 30. FIG. 3 illustrates an embodimentof a frame 32 having a generally rectangular outer perimeter, whichmatches the generally rectangular configuration of the associatedfiltration medium 30. While it may be preferred for the perimeter of theframe 32 to be substantially the same size and shape as the associatedfiltration medium 30, it is also within the scope of the presentdisclosure for the perimeter of the frame 32 to be differently sized(typically larger) and shaped from the associated filtration medium 30.

As shown in FIG. 3, the frame 32 may define an opening or aperture 34,which may be centrally or non-centrally located and either the sameshape as the outer perimeter of the frame 32 (as in FIG. 3) or adifferent shape. In other embodiments, the frame may define a pluralityof openings or apertures, which may be similarly or differentlyconfigured. In a preferred embodiment, the frame 32 is formed of amaterial through which the biological fluid being filtered will notpass, in which case the opening 34 or openings allow for the flow offluid through the frame 32.

As described above, the frame 32 may be formed of a material throughwhich the biological fluid being filtered will not flow. In oneembodiment, the frame 32 is formed of a PVC material (e.g., the samematerial as is used to form the housing), but other materials may beemployed without departing from the scope of the present disclosure. Theframe 32 may be provided as a single-sheet or single-piece component oras a multi-sheet or multi-piece, stacked component.

The filter assembly 10 may include additional components positionedbetween the walls 12 and 14 of the housing. In the embodiment of FIGS.1-2 and 4, the filter assembly 10 includes a pre-filter 36 at leastpartially positioned between the walls 12 and 14 of the filter housing.Preferably, the pre-filter 36 is fully positioned within the filterhousing when the filter assembly 10 is fully assembled (as in FIG. 1),between the filtration medium 30 and the inlet or first side 12 of thefilter housing.

The pre-filter 36 may be variously configured, but is preferablyconfigured as a planar or sheet-like component with a shape that iscongruent to the filtration medium 30. In the illustrated embodiment,the pre-filter 36 has a generally rectangular configuration, whichmatches the generally rectangular configuration of the associatedfiltration medium 30 and frame 32. While it may be preferred for theperimeter of the pre-filter 36 to be substantially the same size andshape as the filtration medium 30, it is also within the scope of thepresent disclosure for the perimeter of the pre-filter 36 to bedifferently sized and shaped from the perimeter of the associatedfiltration medium 30.

The pre-filter 36 is configured to allow the passage of biological fluidtherethrough. Preferably, the pre-filter 36 has different filtrationproperties (e.g., porosity) than the associated filtration medium 30. Inone embodiment, the pre-filter 36 has larger pores than the associatedfiltration medium 30. If the filter assembly 10 is provided as aleukofilter, the pre-filter 36 may be configured to removemicroaggregates from the biological fluid prior to the fluidencountering the filtration medium 30. In such an application, it may beadvantageous for the pre-filter 36 to be comprised of a polyethyleneterephthalate (“PET”) material. In other applications, other materialcompositions may be employed. The pre-filter 36 may be provided as asingle-sheet or single-piece component or as a multi-sheet ormulti-piece, stacked component.

In an alternative embodiment, which is illustrated in FIG. 5, the filterassembly 10 a includes the same components as the embodiment of FIGS.1-4, but with an additional post-filter 38 at least partially positionedbetween the walls 12 and 14 of the filter housing. Preferably, thepost-filter 38 is fully positioned within the filter housing when thefilter assembly 10 a is fully assembled. The post-filter 38 may bevariously secured within the filter housing, such as being securedbetween the frame 32 and the outlet or second side 14 of the filterhousing. Alternatively, the post-filter may be positioned or seatedwithin the opening 34 defined by the frame 32, as in the embodiment ofFIG. 3A. Preferably, the post-filter occupies the entirety of theopening 34, but it is also within the scope of the present disclosurefor the post-filter to occupy only a portion of the opening 34. If thepost-filter is mounted within the opening 34 of the frame 32, the outerperimeter of the post-filter may be secured to the frame 32 by adhesionor a weld or a mechanical fastener or any other suitable fixation means.

The post-filter 38 may be variously configured, but is preferablyconfigured as a planar or sheet-like component with a shape that iscongruent to the frame 32. In the illustrated embodiment, thepost-filter 38 has a generally rectangular configuration, which matchesthe generally rectangular configuration of the associated filtrationmedium 30 and frame 32. While it may be preferred for the post-filter 38to be substantially the same size and shape as the outer perimeter ofthe frame 32, it is also within the scope of the present disclosure forthe post-filter 38 to be differently sized and shaped from the perimeterof the associated frame 32.

The post-filter 38 is configured to allow the passage of biologicalfluid therethrough. The post-filter 38 may have filtration properties(e.g., porosity) that are either the same as or different from those ofthe associated filtration medium 30. In one embodiment, the post-filter38 is formed of the same material as the associated filtration medium 30(e.g., PBT), in which case the post-filter 38 may be distinguished fromthe filtration medium 30 by the presence of the frame 32 positionedtherebetween. Depending on the material composition and configuration ofthe post-filter 38, it may provide any of a number of functions,including filtration-improvement functions (e.g., acting as a spacer ormanifold if the associated outlet port omits an inwardly projectingspacer) and/or manufacturability-improvement features. The post-filter38 may be provided as a single-sheet or single-piece component or as amulti-sheet or multi-piece, stacked component.

In an alternative embodiment, the post-filter may be provided as a meshor mesh-like layer. As used herein, the term “mesh” refers to asemi-permeable layer with material present in a grid or web or crossedarrangement, such as shown in FIG. 3A as component 38 a. The mesh 38 amay be formed according to any suitable method, resulting in a meshhaving a varying thickness (referred to herein as a “three-dimensional”mesh) or a mesh having a generally uniform thickness (referred to hereinas a “two-dimensional” or “planar” mesh). If provided as athree-dimensional mesh, the mesh may be formed of overlapping or wovenstrands or strips of material. If provided as a two-dimensional mesh,the mesh may be defined by non-woven, non-overlapping strands or stripsof material present in a plane.

The material of the mesh 38 a defines openings or voids through whichfiltered fluid passes before exiting the filter assembly 10 via theoutlet port 20, 28. The mesh 38 a of FIG. 3A is shown with generallydiamond-shaped openings or voids, but it is within the scope of thepresent disclosure for the openings or voids to be differently shaped(e.g., a regular shape, such as generally square or rectangular orcircular or triangular or pentagonal or hexagonal, or an irregularshape). A primary purpose of the mesh 38 a may be to act as a manifoldwhich separates the filtration medium 30 from the outlet side 14 of thefilter housing, while allowing filtered fluid to freely flow from thefiltration medium 30 to the outlet port 20, 28. Accordingly, the voidsmay be relatively large to provide a mesh 38 a having a porosity that isgreater than the porosity of the filtration medium 30. However, if thevoids are too large, it is possible for the outlet side 14 of the filterhousing to press against the filtration medium 30 during use, therebymaking it more difficult for filtered fluid to flow out of the filterassembly 10. Thus, it may be preferred for the mesh 38 a to have anintermediate porosity, with voids that are large enough to allowsubstantially free flow of filtered fluid out of the filter assembly 10,but not so large as to negate the desired manifold effect. In oneexemplary embodiment, the voids are generally rectangular or square ordiamond-shaped, each having a height and width in the range ofapproximately 0.5-20 mm, with the mesh 38 a having a thickness in therange of approximately 0.5-4 mm.

Alternatively, rather than characterizing the porosity of the mesh 38 ain terms of the size and shape of its voids, it is also possible tocharacterize its porosity in terms of its permeability properties. Forexample, at a pressure difference of 250 Pa (2500 dyne/cm²) the mesh 38a may have a Frazier (air) permeability of approximately 899 cm³/s·cm²(which is a raw value for a mesh 38 a having a thickness ofapproximately 1.6 mm, which may be normalized to approximately 143.8cm²/s for a mesh 38 a having a thickness of 1 cm) or an air permeabilityin the range of approximately 800 cm³/s·cm²-2000 cm³/s·cm² (which is arange of raw values for a mesh 38 a having a thickness of approximately1.6 mm, which may be normalized to a range of approximately 40 cm²/s-800cm²/s for a mesh 38 a having a thickness of approximately 1 cm), but itis also within the scope of the present disclosure for the mesh 38 a tohave an air permeability that lies outside of this range.

The permeability of the mesh 38 a may also be characterized in terms ofits permeability properties using Darcy's law. According to Darcy's law,the velocity of flow through a porous medium may be expressed by thefollowing equation:

${v = {\frac{- k}{\mu}\bigtriangledown \; P}},$

in which v is velocity, k is the permeability of the medium (alsoreferred to as the Darcy's law constant), μ is the dynamic viscosity,and ∇P is the pressure gradient.

In one exemplary embodiment, in which the mesh 38 a has a permeabilityof approximately 899 cm³/s·cm² at a thickness of 1.6 mm at a pressuredifference of 250 Pa (2500 dyne/cm²), the Darcy's law constant of themesh 38 a was determined to be approximately 1052 μm². In anotherembodiment, the Darcy's law constant of the mesh 38 a may be in therange of 293 to approximately 5852 μm², but it is also within the scopeof the present disclosure for the mesh 38 a to have a Darcy's lawconstant that lies outside of this range.

The mesh 38 a may have a generally uniform porosity or permeability,with generally uniform voids arranged in a uniform pattern, or may havea non-uniform porosity or permeability, with differently sized and/orshaped voids in a uniform or non-uniform pattern or generally uniformvoids arranged in a non-uniform pattern.

The mesh 38 a may be formed of any suitable material or materials suchas, but not limited to, PVC. If the filter assembly 10 is provided withboth a frame 32 and a mesh 38 a, the frame 32 and mesh 38 a may beseparate components that are joined to each other (e.g., by welding oran adhesive or any other suitable method) prior to being incorporatedinto the filter assembly 10 or may remain separate. While the frame 32and mesh 38 a may be formed of different materials, the frame 32 and themesh 38 a are preferably formed of the same material, with the two beingincorporated together as a unitary or integrated or single componentformed by a molding process or any other suitable method. As shown inFIG. 3A, when the filter assembly 10 includes both a frame 32 and a mesh38 a, the mesh 38 a is preferably positioned or seated or defined withinthe opening 34 defined by the frame 32. Preferably, the mesh 38 aoccupies the entirety of the opening 34, but it is also within the scopeof the present disclosure for the mesh 38 a to occupy only a portion ofthe opening 34. The composite frame 32 and mesh 38 a component of FIG.3A may be referred to herein as a mesh element.

In another embodiment, rather than pairing the mesh 38 a with a frame32, a filter assembly may be provided with only a mesh 38 a between thefiltration medium 30 and the outlet side 14 of the filter housing. Ifonly a mesh 38 a is provided, the mesh 38 a may be configured tofree-float with respect to the other components of the filter assembly(i.e., positioned inward of the seals of the filter assembly) or befully secured within the filter assembly (e.g., having a perimeter thatis fully present within one or more seals of the filter assembly) or bepartially secured within the filter assembly (e.g., having only aportion of the perimeter of the mesh 38 a positioned within one or moreseals of the filter assembly).

The filter assembly 10, 10 a includes a seal 40 (FIGS. 1, 4, and 5),which joins the two walls 12 and 14 of the filter housing, as well asthe filtration medium 30 and the frame 32. If provided, the seal 40 mayalso join the other interior components of the filter assembly 10, 10 a(i.e., the pre-filter 36 and/or the post-filter 38). The seal 40 may beformed by any suitable sealing process, such as the application ofpressure and radio-frequency heating to the two walls 12 and 14 of thefilter housing and the interior components of the filter assembly 10, 10a positioned therebetween (collectively identified at 42 in FIG. 6A).Preferably, the seal 40 forms a complete seal at or adjacent to theperimeters of the interior components 42 of the filter assembly 10, 10 ato prevent the biological fluid from “shortcutting” the interiorcomponents 42 (i.e., passing from the inlet port 18 to the outlet port20, 28 without passing through all of the interior components 42 of thefilter assembly 10, 10 a.

Prior to forming the seal 40, the layers of a multi-layer interiorcomponent of the filter assembly 10, 10 a (e.g., the layers of amulti-layer filtration medium 30) and/or two or more of the interiorcomponents of the filter assembly 10, 10 a (e.g., the filtration medium30, the frame 32, the pre-filter 36, and/or the post-filter 38) may besealed together at or adjacent to their peripheral edges. Thus, the seal40 may be formed using either a two-step method, wherein a peripheralseal is first formed within or amongst the interior components of thefilter assembly 10, 10 a and then the peripheral seal is joined to thefilter housing (and any interior components of the filter assembly notincluded within the peripheral seal), or by a one-step method in whichthe filter housing and the interior components 42 of the filter assembly10, 10 a are joined together simultaneously.

A second or outer seal 44 may also be provided (FIGS. 1, 4, and 5),spaced outwardly of the first seal 40. If provided, the outer seal 44may join only the two walls 12 and 14 of the filter housing to eachother. Alternatively, the frame 32 may also be included in the outerseal 44, between the walls 12 and 14 of the filter housing. Preferably,the outer seal 44 forms a complete seal around the inner seal 40 toprevent leakage of the biological fluid out of the filter assembly 10,10 a.

Similar to the inner seal 40, the outer seal 44 may be formed by theapplication of pressure and radio-frequency heating to the two walls 12and 14 of the filter housing or by a different sealing process. Theseals 40 and 44 may be formed in sequential sealing processes, which isrepresented in FIGS. 6A-6C, with FIG. 6B representing a step in whichthe inner seal 40 is formed and FIG. 6C representing a step in which theouter seal 44 is formed. Alternatively, the inner and outer seals 40 and44 may be formed simultaneously, in a single sealing process, which canbe understood as proceeding directly from an assembling or stackingstage (FIG. 6A) to a dual-sealing stage (FIG. 6C).

If two seals 40 and 44 are provided, there may or may not be an unsealedarea 46 between them. If there is an unsealed area 46 between the twoseals 40 and 44, the outer perimeter of the filtration medium 30 and theframe 32 (and, if provided, the pre-filter 36 and the post-filter 38)may be positioned therein, as shown in FIGS. 4 and 5. By such aconfiguration, the unsealed area 46 provides the filter assembly 10, 10a with a softened or cushioned periphery. If provided, the cushionedperiphery provides enhanced protection against damage to tubing and bagsof the associated fluid processing set if the bags, tubing, and filterassembly 10, 10 a of the set are centrifuged.

As described above, the filter housing may be formed of a pair offlexible sheets (FIGS. 6A-6C) or a single sheet of tubular material 16(FIGS. 7A-7C) or a single sheet of material that is folded in half ontoitself, with only minor variations between the manufacturing methodsthereof. For example, if the filter housing is formed using two sheetsof material, the interior components of the filter assembly arepositioned therebetween prior to forming the seals. In contrast, if thefilter housing is formed using a single sheet of tubular material 16,the interior components 42 of the filter assembly 10 b may be insertedinto an open interior defined by the housing sheet 16 (FIG. 7A) prior tothe seals 40 and 44 being formed (FIGS. 7B and 7C). If the filterhousing is formed from a single sheet of material that is folded ontoitself, the interior components of the filter assembly are positionedbetween the two portions of the sheet that are folded into facingrelationship prior to the seals being formed.

Another manufacturing difference is related to the extent of the outerseal 44 along the edges of the filter housing. In particular, if thefilter housing is formed from two sheets of material, it is preferableto form the outer seal 44 along all of the edges of the housing sheets.In contrast, if the filter housing is formed from a single sheet ofmaterial, the outer seal 44 need not be formed along all of the edges ofthe housing. For example, if the filter assembly is formed by insertingthe interior components of the filter assembly between folded portionsof a single housing sheet, the outer seal may be formed at only thethree facing, overlapping edge pairs, without forming the outer seal atthe folded edge. Similarly, the outer seal may be formed at only the twoopposing edges 48 and 50 (FIGS. 7A-7C), without forming the outer sealover the entire outer perimeter of the filter housing, when the filterhousing is formed of a tubular sheet of material 16.

FIG. 8 illustrates a sealing die or electrode 52 provided according toknown design. A sealing die 52 of the type shown in FIG. 8 (when used incombination with an opposed or facing sealing die that is notillustrated, but may be a mirror image of the illustrated sealing die52) may be used to press the layers of the filter assembly together andmelt at least certain layers to cause the layers between the sealingdies to become sealed together. When sealing dies 52 of the type shownin FIG. 8 are used to form an inner seal 40, filtration medium 30positioned between the sealing dies 52 is compressed, but remainspositioned between the inlet and outlet sides 12 and 14 of the resultinginner seal 40. If the filtration medium 30 is formed of a generallyopaque material, such as PBT, the resulting inner seal 40 will begenerally opaque (i.e., not substantially transparent or translucent) aswell.

While known sealing dies of the type shown in FIG. 8 may be used to forman inner seal 40, it may be preferred to use a sealing die having adifferent profile to form the inner seal. For example, FIG. 9illustrates a sealing die or electrode 54 that may be used (incombination with an opposed or facing sealing die that is notillustrated, but may be a mirror image of the illustrated sealing die54) to form an inner seal. Compared to the sealing die 52 of FIG. 8, thesealing die 54 may have the same or a similar width (e.g., approximately5.5 mm), but a different cross-sectional profile. For example, thesealing die 52 of FIG. 8 has a substantially flat or planar contactsurface 56 extending between inner and outer corners 58 having arelatively small radius (e.g., approximately 1.5 mm in one embodiment).In contrast, the sealing die 54 of FIG. 9 has a generally semi-circularcontact surface 60 with a relatively large radius (e.g., approximately2.75 mm in one embodiment). In use, sealing dies 52 of the type shown inFIG. 8 are typically brought within approximately 1.4-1.8 mm of eachother to form a seal, whereas sealing dies 54 of the type shown in FIG.9 may be brought closer together (e.g., within approximately 1.0-1.4 mmin one embodiment) to form a seal. The other sealing parameters (e.g.,pressure, energy, and temperature) may be substantially the same whenusing sealing dies of the type shown in FIG. 8 or FIG. 9.

When sealing dies 54 of the type shown in FIG. 9 are used according tothe foregoing method to form an inner seal, the resulting inner seal 40a (FIG. 11) will have a central section that is at least substantially(but more preferably completely) free of filtration medium 30. While thesealing dies 54 and component filter materials are selected to result ina central section that is substantially free of filtration medium 30along the entire extent of the inner seal 40 a (i.e., along the entireperimeter that the inner seal 40 a defines within the filter assembly),eccentricities in individual manufacturing processes may result in traceamounts of filtration medium 30 present along the inner seal 40 a.Accordingly, it should be understood that the central section of theinner seal 40 a, in practice, may have small amounts of filtrationmedium 30 present therein, but the central section of the inner seal 40a is preferably at least substantially free of filtration medium 30along at least a majority of the extent of the inner seal 40 a. If thefiltration medium 30 is formed of a generally opaque material, while theother layers present in the inner seal 40 a are generally transparent,the complete or substantial exclusion of the filtration medium 30 willresult in an inner seal 40 a having a central section that is generallytransparent along at least a majority of the extent of the inner seal 40a, but more preferably along the entire extent of the inner seal 40 a.As used herein, the term “central section” refers to a portion of a sealthat is positioned between inner and outer peripheral sections of theseal and is not limited to a section that is centered about the midpointof the seal.

FIGS. 10 and 11 illustrate the formation of an inner seal 40 a (FIG. 11)using sealing dies 54 of the type shown in FIG. 9. In FIGS. 10 and 11,the filter assembly includes inlet and outlet housing walls 12 and 14(which may be formed of a PVC material), with a multiple-layerfiltration medium 30 (which may be formed of a PBT material) positionedtherebetween. A pre-filter 36 (which may be formed of a PET material) ispositioned between the inlet housing wall 12 and the filtration medium30, while a frame 32 (which may be formed of a PVC material) ispositioned between the outlet housing wall 14 and the filtration medium30. Although not illustrated, the frame 32 preferably includes anassociated mesh (as in FIG. 3A), which is positioned inwardly of theinner seal to be formed. While FIGS. 10 and 11 illustrate an inner seal40 a formed in a filter assembly having a pair of housing walls, afiltration medium, a pre-filter, and a post-filter frame, it should beunderstood that an inner seal which is transparent and/or at leastsubstantially omits a filtration medium may be formed in a filterassembly having fewer layers (e.g., only a pair of housing walls and afiltration medium) or more or different layers.

When sealing dies 54 of the type shown in FIG. 9 are used to form theinner seal 40 a, the inlet and outlet housing walls 12 and 14, thefiltration medium 30, and the frame 32 rend to melt, while thepre-filter 36 tends to not melt. Thus, applying pressure to the layersof the filter assembly causes the inlet housing wall 12 to melt, with aportion of the molten inlet housing wall 12 invading the voids of thepre-filter 36 to form an intermingled layer 62 within the inner seal 40a. Rather than invading the voids of the pre-filter 36 and entering theintermingled layer 62, the molten filtration medium 64 tends to bepushed aside, out of a central section 66 of the inner seal 40 a andinto inner and outer peripheral sections 68 and 70 of the inner seal 40a. The space formerly occupied by the filtration medium 30 in thecentral section 66 of the inner seal 40 a is replaced by an aggregate 72of melted outlet housing wall 14 and frame 32 material. The aggregate 72may be pressed into the intermingled layer 62 in the central section 66of the inner seal 40 a, thereby meeting molten inlet housing wall 12within the confines of the pre-filter 36. Although the molten filtrationmedium 64 is completely or at least substantially excluded from thecentral section 66 of the inner seal 40 a, it may tend to interminglewith the adjacent layers (i.e., the pre-filter 36 and frame 32) and/orthe intermingled layer 62 and aggregate 72 to hold the molten filtrationmedium 64 within place in the peripheral sections 68 and 70 of the innerseal 40 a. The intermingled interface between the molten filtrationmedium 64 and adjacent layers tends to be extremely thin (e.g., on theorder of approximately 50-60 micrometers or less, but preferably lessthan 150 micrometers), but is sufficiently strong to maintain thefiltration medium 30 in place within the filter assembly. Outside of theperipheral sections 68 and 70 of the inner seal 40 a, the various layersof the filter assembly may remain un-melted, thereby maintaining theirindependence from the adjacent layers.

With respect to FIG. 11, the dimensions of the various formations withinthe inner seal 40 a will typically vary, depending on the nature of thematerials used and the exact sealing method. However, in one exemplaryembodiment, the inlet housing wall 12 has a thickness of approximately90-250 micrometers in the central section 66 of the inner seal 40 a, theintermingled layer 62 has a thickness of approximately 170-300micrometers in the central section 66, and the aggregate 72 has athickness of approximately 0.84-1.5 mm in the central section 66. Thecentral section 66 itself may have a width of approximately 0.15-8 mm(e.g., approximately 240 micrometers-1.5 mm in one embodiment orapproximately 1.0 mm in a preferred embodiment) and a thickness ofapproximately 0.2-7 mm (e.g., approximately 1.2-2 mm in one embodiment).In the peripheral sections 68 and 70 of the inner seal 40 a, the inlethousing wall 12 may having a greater thickness (e.g., approximately130-350 micrometers), the intermingled layer 62 may have a wider rangeof thicknesses (e.g., approximately 150-400 micrometers), the aggregate72 may have a lesser thickness (e.g., approximately 170-650 micrometers)than in the central section 66 of the inner seal 40 a. The thickness ofthe molten filtration medium 64 may vary in the peripheral sections 68and 70, typically being thinner adjacent to the central section 66 andthicker at the opposite end of the peripheral section 68, 70. Forexample, in one embodiment, the molten filtration medium 64 may have amaximum thickness of approximately 1.2 mm and taper to at leastsubstantial non-existence in the central section 66 of the inner seal 40a. The width of each peripheral section 68, 70 may be in the range ofapproximately 0.5-5 mm in an exemplary embodiment or approximately 2.5mm in a more preferred embodiment. The length of the interface overwhich the molten filtration medium 64 is intermingled with the adjacentlayers may vary, but in one embodiment is approximately 3.5-4.6 mm, asmeasured along the edges of the molten filtration medium 64 facing theinlet housing wall 12, the outlet housing wall 14, and the centralsection 66.

The various dimensions of the filter assembly in and around the innerseal 40 a may be measured using any suitable method. In one exemplaryembodiment, a cut is made perpendicular to the seal 40 a (i.e., from aninner portion of a seal to an outer portion of the seal). Thecross-section of the seal 40 a formed by the cut is then examined usinga magnification device, such as an electron scanning microscope or adigital microscope. The optimal level of magnification may vary,depending on the portion of the seal 40 a being observed and thedimension to be measured. For example, it may be suitable to use a 10×magnification to observe and measure certain larger dimensions (e.g.,the width of the seal 40 a), whereas a greater magnification (e.g., 30×or more) may be preferred for measuring smaller dimensions (e.g., thethickness of the intermingled interface between the molten filtrationmedium 64 and the adjacent layers).

FIG. 11 and the above dimensions assume a generally symmetrical innerseal 40 a, formed by a substantially symmetrical sealing die 54, but itis also within the scope of the present disclosure for an inner sealwhich is generally transparent and/or at least substantially omitsfiltration medium to be non-symmetrical. For example, FIG. 12illustrates an alternative embodiment of a sealing die or electrode 74that may be used to form an inner seal with a central section that istransparent and/or at least substantially omits a filtration medium. Thesealing die 74 of FIG. 12 may be understood as a combination of thesealing dies 52 and 54 of FIGS. 8 and 9, with a generally flat or planarcontact surface 76 that extends between a first or inner corner 78 and asecond or outer corner 80. The second corner 80 is positioned lower thanthe first corner 78 (when the sealing die 74 is oriented as the uppersealing die of a pair of opposing or facing sealing dies), such that thecontact surface 76 of the sealing die 74 is angled or inclined orslanted with respect to horizontal. The first corner 78 may have arelatively small radius (e.g., comparable to the radius of the corners58 of the sealing die 52 of FIG. 8), while the second corner 80 may havea larger radius (e.g., comparable to the radius of the contact surface60 of the sealing die 54 of FIG. 9). The sealing die 74 of FIG. 12 (whenused in combination with an opposing or facing sealing die that is notillustrated, but may be a mirror image of the illustrated sealing die74) may be used to form an inner seal. The sealing die 74 of FIG. 12 maybe wider (e.g., approximately 50% wider) than the sealing dies 52 and 54of FIGS. 8 and 9, in which case the resulting inner seal will be widerthan a seal formed using one of the sealing dies 52 and 54.

On account of the shape of the sealing die 74 of FIG. 12, the resultinginner seal will have a central section that is positioned in thevicinity of the second corner 80 of the sealing die 74, rather thanbeing centered about a midpoint of the seal. The seal will have onerelatively narrow peripheral section (to the right of the centralsection in the orientation of FIG. 12) that is comparable to one of theperipheral sections 68, 70 of FIG. 11 and a relatively wide peripheralsection (to the left of the central section in the orientation of FIG.12) that is more comparable to a seal formed using sealing dies 52 ofthe type shown in FIG. 8). The first corner 78 of the sealing die 74 maybe referred to as an inner corner because it may be preferred for thesealing die 74 to be oriented such that the first corner 78 ispositioned closer to the center of the layers of the filter assemblythan the second corner 80 is when the seal is being formed. However, itis also within the scope of the present disclosure for the sealing die74 to be oriented such that the second corner 80 is positioned closer tothe center of the layers of the filter assembly than the first corner 78is when the seal is formed.

As described above, an inner seal formed according to the presentdisclosure may have a central section that is generally transparent ormore light-transmissive than a seal having filtration medium presenttherein. According to one manner of assessing the transparency of thecentral section of an inner seal, the light transmissivity of thecentral section of the inner seal may be compared to the lighttransmissivity of an associated outer seal 44 (if provided) using aconventional light detector. For example, in an exemplary testprocedure, a Model ILT1400A radiometer/photometer from InternationalLight Technologies of Peabody, Mass. was used to measure the lighttransmissivity of three filter assemblies, one manufactured according tothe methods described herein and the other two manufactured according toconventional design. A light source emitting a red laser having awavelength of approximately 635 nm was positioned approximately 19inches away from a photodetector, with the laser focused off center ofthe photodetector to prevent photodetector saturation. A baselinereading of 852 kw/cm² was measured with no filter assembly positionedbetween the light source and the photodetector. Then, a filter assemblywas placed onto the photodetector, with the outer seal positioned at thefocus of the laser, and a reading was taken to determine the lighttransmissivity of the outer seal. The filter assembly was thenrepositioned to place the inner seal at the focus of the laser and areading was taken to determine the light transmissivity of the innerseal. In the exemplary test procedure, readings were taken at multiplelocations along the outer and inner seals, with one reading being takenat each of the upper, lower, left, and right edges of each seal. Thesame procedure was then repeated for two other filter assemblies.

The outer seal includes only the inlet and outlet housing walls, whichare preferably formed of a generally transparent material. In contrast,the central section of the inner seal includes at least the inlet andhousing walls, and may also include other layers (e.g., a pre-filter andpost-filter), but with no or substantially no filtration medium. Onaccount of typically having more layers and a greater thickness than theouter seal, the central section of the inner seal will typically have alower light transmissivity than the outer seal, as demonstrated by theresults of the exemplary test procedure. For example, the outer seal ofa filter assembly manufactured according to the present disclosure wasfound to transmit approximately 81-84% of the red laser light, whereasthe inner seal of the filter assembly was found to transmitapproximately 7-33% of the red laser light. Comparing the lighttransmissivity of each side of the inner seal to the corresponding sideof the outer seal, it was found that the inner seal had a lighttransmissivity of approximately 8-40% of the light transmissivity of theouter seal. For a first conventional biological fluid filter assembly,the light transmissivity of the outer seal was measured to beapproximately 73-84%, while the light transmissivity of the inner sealwas measured to be approximately 3-4% (i.e., approximately 3-5% of thelight transmissivity of the outer seal). For another conventionalbiological fluid filter assembly, the light transmissivity of the outerseal was measured to be approximately 67-71%, while the lighttransmissivity of the inner seal was measured to be approximately 2-3%(i.e., approximately 3-4% of the light transmissivity of the outerseal). Thus, based on the exemplary test procedure, it was found thatthe relative light transmissivity of the inner seal of a filter assemblymanufactured according to the present disclosure (i.e., the lighttransmissivity of the inner seal divided by the light transmissivity ofthe outer seal) was found to be at least approximately 100% greater thanthe relative light transmissivity of the inner seal of a conventionalfilter assembly.

If the relative light transmissivity of the central section of the innerseal (i.e., the light transmissivity of the central section of the innerseal divided by the light transmissivity of the outer seal) is above aparticular percentage (e.g., above approximately 8% or aboveapproximately 20% or above approximately 30%), the central section ofthe inner seal may be considered to be generally transparent, as theterm is used herein. The term “generally transparent” as used inconnection with the inner seal is intended as a measure of the lighttransmissivity of the inner seal, meaning that an inner seal that istranslucent, but with a light transmissivity that is within a particularpercentage of the light transmissivity of an associated outer seal, maybe considered to be “generally transparent.” Other methods for measuringthe transparency of the inner seal may also be employed withoutdeparting from the scope of the present disclosure. For example, if thefilter assembly does not include an outer seal, then the lighttransmissivity of the central section of the inner seal may be comparedto the light transmissivity of two sheets of material that correspond tothe sheets of material used to form the inlet and outlet housing wallsof the filter assembly.

While several embodiments of filter assemblies and methods ofmanufacturing such filter assemblies are described herein, it should beunderstood that variations may be made to the described and illustratedfilter assemblies and methods without departing form the scope of thepresent disclosure. For example, rather than including only one or twoperipheral seals, filter assemblies according to the present disclosuremay be provided with more than two peripheral seals. A third peripheralseal, positioned outwardly of the second or outer seal 44, may beperforated or scored or otherwise weakened to define a tear strip ortear seal between a filter assembly and a consecutively manufacturedfilter assembly. By such a configuration, a plurality of filterassemblies may be manufactured using elongated rolls of material, withadjacent filter assemblies being torn along the third or outermostperipheral seal to separate the filter assemblies.

EXAMPLES

Without limiting any of the foregoing, the subject matter describedherein may be found in one or more apparatus or methods. For example,according to a first exemplary configuration, a biological fluid filterassembly includes first and second flexible housing walls. A filtrationmedium is at least partially positioned between the two housing walls. Aseal joins the housing walls and passes through the filtration medium todefine a perimeter within the biological fluid filter assembly, butthere is substantially no filtration medium present in a central sectionof the seal along at least a majority of the extent of the perimeterdefined by the seal.

A second exemplary configuration of a biological fluid filter assemblyincludes a configuration in accordance with the preceding exemplaryconfiguration, in which the first and second walls are generallytransparent, the filtration medium is generally opaque, and the centralsection of the seal is generally transparent along at least a majorityof the extent of the perimeter defined by the seal.

A third exemplary configuration of a biological fluid filter assemblyincludes a configuration in accordance with the preceding exemplaryconfiguration, in which the filtration medium is present in generallyopaque peripheral sections of the seal.

A fourth exemplary configuration of a biological fluid filter assemblyincludes a configuration in accordance with any one of exemplaryconfigurations 1-3, in which a pre-filter is at least partiallypositioned between the filtration medium and the first housing wall,with the seal joining the housing walls and the pre-filter.

A fifth exemplary configuration of a biological fluid filter assemblyincludes a configuration in accordance with any one of exemplaryconfigurations 1-4, in which a support member is at least partiallypositioned between the filtration medium and the second housing wall,with the seal joining the housing walls and the support member.

A sixth exemplary configuration of a biological fluid filter assemblyincludes a configuration in accordance with any one of exemplaryconfigurations 1-5, in which a mesh is at least partially positionedbetween the filtration medium and the second housing wall.

A seventh exemplary configuration of a biological fluid filter assemblyincludes a configuration in accordance with the preceding exemplaryconfiguration, in which the mesh is part of a mesh element. The meshelement includes the mesh integrally formed with a frame that surroundsthe mesh to define a perimeter of the mesh element. The seal joins thehousing walls and the frame.

An eighth exemplary configuration of a biological fluid filter assemblyincludes first and second flexible housing walls. A filtration medium isat least partially positioned between the two housing walls. Apost-filter mesh is at least partially positioned between the filtrationmedium and the second housing wall. A seal joins the housing walls.

A ninth exemplary configuration of a biological fluid filter assemblyincludes a configuration in accordance with the preceding exemplaryconfiguration, in which the seal joins the housing walls and thepost-filter mesh.

A tenth exemplary configuration of a biological fluid filter assemblyincludes a configuration in accordance with the eighth exemplaryconfiguration, in which a frame is positioned between the filtrationmedium and the second housing wall, with the post-filter mesh beingintegrally formed with the frame.

An eleventh exemplary configuration of a biological fluid filterassembly includes a configuration in accordance with the precedingexemplary configuration, in which the seal joins the housing walls andthe frame.

A twelfth exemplary configuration of a biological fluid filter assemblyincludes a configuration in accordance with the preceding exemplaryconfiguration, in which the frame is comprised of the same material asthe second housing wall and the frame and second housing wall are meltedtogether in at least a portion of the seal.

A thirteenth exemplary configuration of a biological fluid filterassembly includes a configuration in accordance with any one ofexemplary configurations 8-12, in which a pre-filter is at leastpartially positioned between the filtration medium and the first housingwall, with the seal joining the housing walls and the pre-filter.

A fourteenth exemplary configuration of a biological fluid filterassembly includes a flexible housing having first and second walls. Thefirst wall includes an inlet port and the second wall includes an outletport, with the first and second walls being made of a plastic material.A filtration medium for removing at least one substance from abiological fluid is at least partially positioned between the inlet andoutlet ports, with a pre-filter at least partially positioned betweenthe inlet port and the filtration medium. A mesh element having a meshintegrally formed with a frame is at least partially positioned betweenthe outlet port and the filtration medium, with the mesh element beingmade of the plastic material. A seal is formed by integrating a sectionof the filtration medium at or adjacent to its perimeter, a section ofthe pre-filter at or adjacent to its perimeter, a section of the frameof the mesh element, and a section of the first and second walls at oradjacent to their perimeter and over their entire perimeter. The sealincludes a central section consisting of a layer consisting only of theplastic material of the first wall and having a thickness in the rangeof approximately 90-100 micrometers, an intermingled layer in which theplastic material of at least the first wall is intermingled with thepre-filter and having a thickness in the range of approximately 170-200micrometers, and an aggregate in which the plastic material of at leastthe second wall and the frame are intermingled and having a thickness inthe range of approximately 840-900 micrometers.

A fifteenth exemplary configuration of a biological fluid filterassembly includes a configuration in accordance with the precedingexemplary configuration, in which the seal also includes a pair ofperipheral sections, with the peripheral sections positioned at oppositesides of the central section. Each peripheral section includes a layerconsisting only of the plastic material of the first wall, anintermingled layer in which the plastic material of at least the firstwall is intermingled with the pre-filter, an intermingled interface inwhich molten filtration medium is intermingled with the pre-filter, alayer consisting only of molten filtration medium, a second intermingledinterface in which molten filtration medium is intermingled with theframe, a second intermingled layer in which the plastic material of atleast the second wall and the frame are intermingled, and a layerconsisting only of the plastic material of the second wall. Theintermingled interface and the second intermingled interface of theperipheral sections each have a thickness of less than 150 micrometers.

A sixteenth exemplary configuration of a biological fluid filterassembly includes a configuration in accordance with the precedingexemplary configuration, in which the filtration medium transitions froma molten state at an end of each peripheral section adjacent to thecentral section of the seal to a non-molten state at an opposite end ofeach peripheral section.

A seventeenth exemplary configuration of a biological fluid filterassembly includes a configuration in accordance with any one ofexemplary configurations 14-16, in which the plastic material ispolyvinyl chloride.

An eighteenth exemplary configuration of a biological fluid filterassembly includes first and second flexible housing walls. A filtrationmedium is at least partially positioned between the two housing walls. Apost-filter mesh having a Darcy's Law permeability constant in the rangeof 293 to approximately 5852 μm² is at least partially positionedbetween the filtration medium and the second housing wall. A seal joinsthe housing walls.

A nineteenth exemplary configuration of a biological fluid filterincludes a configuration in accordance with the preceding exemplaryconfiguration, in which the post-filter mesh has a Darcy's Lawpermeability constant of approximately 899 μm².

In another aspect of this subject matter, a first exemplary method ofmanufacturing a biological fluid filter assembly includes providingfirst and second flexible housing walls. At least a portion of afiltration medium is positioned between the housing walls. A seal thatpasses through the filtration medium is formed to join the housing wallsand define a perimeter within the biological fluid filter assembly, withsubstantially no filtration medium being present in a central section ofthe seal along at least a majority of the extent of the perimeterdefined by the seal.

A second exemplary method of the present subject matter includes amethod in accordance with the preceding exemplary method, in which thehousing walls are generally transparent, the filtration medium isgenerally opaque, and the seal has a generally transparent centralsection along at least a majority of the extent of the perimeter definedby the seal.

A third exemplary method of the present subject matter includes a methodin accordance with the preceding exemplary method, in which the seal hasgenerally opaque peripheral sections in which the filtration medium ispresent.

A fourth exemplary method of the present subject matter includes amethod in accordance with any one of exemplary methods 1-3, in which atleast a portion of a pre-filter is positioned between the filtrationmedium and the first housing wall, with the seal joining the housingwalls and the pre-filter.

A fifth exemplary method of the present subject matter includes a methodin accordance with any one of exemplary methods 1-4, in which at least aportion of a support member is positioned between the filtration mediumand the second housing wall, with the seal joining the housing walls andthe support member.

A sixth exemplary method of the present subject matter includes a methodin accordance with any one of exemplary methods 1-5, in which at least aportion of a mesh is positioned between the filtration medium and thesecond housing wall.

A seventh exemplary method of the present subject matter includes amethod in accordance with the preceding exemplary method, with the meshbeing integrally formed with a support member defining a frame. The sealjoins the housing walls and the frame.

It will be understood that the embodiments and examples described aboveare illustrative of some of the applications of the principles of thepresent subject matter. Numerous modifications may be made by thoseskilled in the art without departing from the spirit and scope of theclaimed subject matter, including those combinations of features thatare individually disclosed or claimed herein. For these reasons, thescope hereof is not limited to the above description but is as set forthin the following claims, and it is understood that claims may bedirected to the features hereof, including as combinations of featuresthat are individually disclosed or claimed herein.

1. A biological fluid filter assembly comprising: a flexible housinghaving first and second walls; a filtration medium at least partiallypositioned between the first and second walls of the housing; and a sealjoining the first and second walls of the housing, the seal passingthrough the filtration medium to define a perimeter within thebiological fluid filter assembly, with substantially no filtrationmedium present in a central section of the seal along at least amajority of the extent of the perimeter defined by the seal.
 2. Thebiological fluid filter assembly of claim 1, wherein the first andsecond walls are generally transparent, the filtration medium isgenerally opaque, and the central section of the seal is generallytransparent along at least a majority of the extent of the perimeterdefined by the seal.
 3. The biological fluid filter assembly of claim 2,wherein the filtration medium is present in generally opaque peripheralsections of the seal.
 4. The biological fluid filter assembly of claim1, further comprising a pre-filter at least partially positioned betweenthe filtration medium and the first wall of the housing, wherein theseal joins the first and second walls of the housing and the pre-filter.5. The biological fluid filter assembly of claim 1, further comprising asupport member at least partially positioned between the filtrationmedium and the second wall of the housing, wherein the seal joins thefirst and second walls of the housing and the support member.
 6. Thebiological fluid filter assembly of claim 1, further comprising a meshat least partially positioned between the filtration medium and thesecond wall of the housing.
 7. The biological fluid filter assembly ofclaim 6, wherein the mesh is part of a mesh element in which the mesh isintegrally formed with a frame that surrounds the mesh to define aperimeter of the mesh element, and the seal joins the first and secondwalls of the housing and the frame.
 8. A biological fluid filterassembly comprising: a flexible housing having first and second walls; afiltration medium at least partially positioned between the first andsecond walls of the housing; a post-filter mesh at least partiallypositioned between the filtration medium and the second wall; and a sealjoining the first and second walls of the housing.
 9. The biologicalfluid filter assembly of claim 8, wherein the seal joins the first andsecond walls of the housing and the post-filter mesh.
 10. The biologicalfluid filter assembly of claim 8, further comprising a frame positionedbetween the filtration medium and the second wall, wherein thepost-filter mesh is integrally formed with the frame.
 11. The biologicalfluid filter assembly of claim 10, wherein the seal joins the first andsecond walls of the housing and the frame.
 12. The biological fluidfilter assembly of claim 11, wherein the frame is comprised of the samematerial as the second wall, and the frame and the second wall aremelted together in at least a portion of the seal.
 13. The biologicalfluid filter assembly of claim 8, further comprising a pre-filter atleast partially positioned between the filtration medium and the firstwall of the housing, wherein the seal joins the first and second wallsof the housing and the pre-filter.
 14. A biological fluid filterassembly comprising: a flexible housing having first and second walls,the first wall including an inlet port and the second wall including anoutlet port, wherein the first and second walls are made from a plasticmaterial; a filtration medium for removing at least one substance from abiological fluid, wherein the filtration medium is at least partiallypositioned between the inlet and outlet ports; a pre-filter at leastpartially positioned between the inlet port and the filtration medium; amesh element at least partially positioned between the outlet port andthe filtration medium and comprising a mesh integrally formed with aframe, wherein the mesh element is made from the plastic material; and aseal formed by integrating a section of the filtration medium at oradjacent to a perimeter of the filtration medium, a section of thepre-filter at or adjacent to a perimeter of the pre-filter, a section ofthe frame of the mesh element, and a section of the first and secondwalls at or adjacent to a perimeter of the first and second walls andover the entire perimeter of the first and second walls, wherein theseal comprises a central section consisting of a layer consisting onlyof the plastic material of the first wall and having a thickness in therange of approximately 90-250 micrometers, an intermingled layer inwhich the plastic material of at least the first wall is intermingledwith the pre-filter and having a thickness in the range of approximately170-300 micrometers, and an aggregate in which the plastic material ofat least the second wall and the frame are intermingled and having athickness in the range of approximately 084-1.5 millimeters.
 15. Thebiological fluid filter assembly of claim 14, further comprising a pairof peripheral sections, with the peripheral sections positioned atopposite sides of the central section and each comprising a layerconsisting only of the plastic material of the first wall, anintermingled layer in which the plastic material of at least the firstwall is intermingled with the pre-filter, an intermingled interface inwhich molten filtration medium is intermingled with the pre-filter, alayer consisting only of molten filtration medium, a second intermingledinterface in which molten filtration medium is intermingled with theframe, a second intermingled layer in which the plastic material of atleast the second wall and the frame are intermingled, and a layerconsisting only of the plastic material of the second wall, wherein theintermingled interface and the second intermingled interface each have athickness of less than 150 micrometers.
 16. The biological fluid filterassembly of claim 15, wherein the filtration medium transitions from amolten state at an end of each peripheral section adjacent to thecentral section of the seal to a non-molten state at an opposite end ofeach peripheral section.
 17. The biological fluid filter assembly ofclaim 14, wherein the plastic material is polyvinyl chloride. 18-19.(canceled)
 20. A method for manufacturing a biological fluid filterassembly, comprising: providing a first flexible housing wall and asecond flexible housing wall; positioning at least a portion of afiltration medium between the first and second housing walls; andforming a seal which joins the first and second housing walls and passesthrough the filtration medium to define a perimeter within thebiological fluid filter assembly, with substantially no filtrationmedium present in a central section of the seal along at least amajority of the extent of the perimeter defined by the seal.
 21. Themethod of claim 20, wherein said providing a first flexible housing walland a second flexible housing wall includes providing generallytransparent first and second housing walls, said positioning at least aportion of a filtration medium between the first and second housingwalls includes positioning at least a portion of a generally opaquefiltration medium between the first and second housing walls, and saidforming a seal includes forming a seal having a generally transparentcentral section along at least a majority of the extent of the perimeterdefined by the seal.
 22. The method of claim 21, wherein said forming aseal includes forming a seal having filtration medium present ingenerally opaque peripheral sections of the seal.
 23. The method ofclaim 20, further comprising positioning at least a portion of apre-filter between the filtration medium and the first housing wall,wherein said forming a seal includes forming a seal which joins thefirst and second housing walls and the pre-filter.
 24. The method ofclaim 20, further positioning at least a portion of a support memberbetween the filtration medium and the second housing wall, wherein saidforming a seal includes forming a seal which joins the first and secondhousing walls and the support member.
 25. The method of claim 20,further comprising positioning at least a portion of a mesh between thefiltration medium and the second housing wall.
 26. The method of claim25, wherein said positioning at least a portion of a mesh between thefiltration medium and the second housing wall includes positioning atleast a portion of a mesh integrally formed with a support memberdefining a frame between the filtration medium and the second housingwall, and said forming a seal includes forming a seal which joins thefirst and second housing walls and the frame.